Objective： The key biomarkers CAV1 and CAV2 of HNSCC were screened based on bioinformatics methods, and their expression in HNSCC and clinical prognostic value were explored. Methods: In this study, we first compared the differential expression of caveolins and cavins in HNSCC based on the GEPIA database, and then simultaneously analyzed the relationship between the differential genes and clinical phenotypes in the caveolins and cavins families in the Ualcan platform; compared the relationship between the differential genes associated with the clinical phenotypes and the survival of HNSCC; and in addition performed CAV1 and CAV2 enrichment analysis and immune infiltration analysis were performed. Results: GEPIA database analysis showed significant correlation between CAV1, CAV2, CAVIN2,CAVIN3, etc. Among them, CAV1 and CAV2 were significantly correlated with the clinical phenotype and could significantly affect the survival and prognosis of HNSCC patients. GSEA enrichment analysis showed that CAV1 mainly upregulated IL-17 signaling pathway, PI3K-Akt signaling pathway and NOD-like receptor signaling pathway; CAV2 mainly upregulated NODlike receptor signaling pathway and PI3K-Akt signaling pathway. signaling pathway, PI3K-Akt signaling pathway, and NOD-like receptor signaling pathway; CAV2 mainly up-regulated NODlike receptor signaling pathway and PI3K-Akt signaling pathway; and immune infiltration analysis showed that CAV1 and CAV2 significantly altered the survival and prognosis of HNSCC patients. CAV2 significantly altered the immune microenvironment of HNSCC tumors and correlated with the infiltration of various immune cells. Conclusion: CAV1 and CAV2, which are highly expressed in HNSCC, are independent prognostic factors associated with immune invasion and can be used as candidate prognostic markers for determining immune invasion-related prognosis in patients with HNSCC.